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Area of Science:

  • Microbiology
  • Molecular Biology
  • Pathogenesis

Background:

  • Bacterial pathogens possess temperature-sensing molecules to regulate virulence upon host entry.
  • The population-level dynamics and quantitative outcomes of thermosensing responses remain largely unknown.

Purpose of the Study:

  • To investigate the dynamics and quantitative outcomes of thermosensing in bacterial populations.
  • To elucidate the role of the RovA regulator in Yersinia pseudotuberculosis pathogenicity.

Main Methods:

  • Utilized Yersinia pseudotuberculosis and its thermosensing regulator RovA as a model system.
  • Employed experimental observations and mathematical modeling to analyze the thermoresponsive bistable switch.
  • Observed RovA ON/OFF subpopulations in infected mouse models.

Main Results:

  • Identified RovA as part of a novel thermoresponsive bistable switch generating high- and low-invasive subpopulations.
  • Demonstrated that temperature, regulator synthesis/degradation rates, and nutrient availability modulate bistability.
  • Observed hysteresis in the switch's activation and deactivation, with proteolysis being key to thermosensing.
  • Found that altered RovA ON/OFF ratios in mice reduced colonization and virulence.

Conclusions:

  • The thermoresponsive bistable switch acts as a bet-hedging strategy for bacterial adaptation to host environments.
  • This mechanism is crucial for bacterial survival and pathogenicity within the intestinal tract.
  • Findings suggest novel therapeutic strategies targeting bacterial thermosensing mechanisms.